The regioselective synthesis of sucrose monoesters of fatty acids including lauryl, myristyl, palmityl and stearyl has been reported. Chemical acylation, using a dibutylstannylene complex, affords 6-O-acylsucrose with 3-O-acylsucrose as minor product. Enzymatic acylation of sucrose, using subtilsin, affords 1'-O-acylsucrose and 1',6'-di-O-acylsucrose as a minor product. These acylsucrose derivatives display better critical micellar concentration (CMC) values than the commercial nonionic surfactants. The CMC value is the specific concentration in aqueous solution at which the molecules aggregate in micelles. However, the stearyl derivatives, having the longest fatty chain and expected to display the best CMC values, are water insoluble. The inventors have found that the regioselective introduction of a polar sulfate group into these acyl derivatives improves their water solubility as well as their CMC values.
The direct regioselective synthesis of O-acyl, O-sulfosucrose derivatives can be achieved by regioselective sulfonation of sucrose followed by regioselective acylation, or by regioselective acylation followed by regioselective sulfonation. Introduction of O-sulfo groups is usually done by directly treating hydroxyl groups with a common sulfonation reagent, including complexes of sulfur trioxide and Lewis base, such as N,N-dimethylformamide (DMF), pyridine or trialkylamine. Other sulfonation reagents include sulfuric acid in presence of N,N'-dicyclohexylcarbodiimide or acetic anhydride, piperidine-N-sulfonic acid, and chlorosulfonic acid. The regioselective sulfonation of partially protected monosaccharides and disaccharides proceeds similarly to O-acylation. Sulfonation of the primary position is preferred and the reaction progresses with the formation of isomeric primary monosulfates followed by sulfonation of secondary hydroxyl groups. Dibutylstannanediyl acetals can also be used for the regioselective sulfonation of partially protected monosaccharides and disaccharides using sulfur trioxide-triethylamine complex.
An O-sulfo group can also be introduced regiospecifically by performing the nucleophilic opening of a cyclic sulfate, this method being useful for both regiospecific introduction of nucleophile and sulfo groups. These nucleophilic reactions have high reactivity and the wide variety of available O-nucleophiles (phenolate, amine oxides or benzoate), S-nucleophiles (thiocyanate, thiophenolate), halide nucleophiles (tetraethyl or tetrabutyl ammonium fluoride or chloride), C-nucleophiles (Grignard Reagents, phenylithium, sodium phenylacetylide), and N-nucleophiles (azide and amines). No cyclic sulfate synthesis of unprotected carbohydrates, if particular of sucrose, are known. However, the expected regiospecific opening of a cyclic sulfate makes this approach a very attractive and a potentially powerful way for the regiospecific synthesis of mono-O-sulfosucrose derivatives. Moreover, the use of a nucleophile having a fatty chain might lead to new types of surfactants, in which both hydrophobic and sulfate moities are regiospecifically introduced.
Attempts to synthesize cyclic sulfates of unprotected sugars with sulfuryl chloride and pyridine have been reported. However, the reaction has never been clean and several side products were isolated. For example, reaction of sucrose with sulfuryl chloride at -78.degree. C. affords the 6,6'-dichloro-6,6'-deoxysucrose and 6'-chloro-6'-deoxysucrose in 43% and 29% yield. At room temperature, a complex mixture is formed from which 3',4'-anhydro-1',6'-dichloro-1',6'-dideoxy-.beta.-D-ribo-hexulo-furanoside 2,3-cyclic sulfate is isolated in 17% yield, showing that chlorination occurs as well as inversion of configuration during cyclic sulfate formation. Thus, the reaction of sulfuryl chloride with carbohydrates containing free hydroxyl groups has become a well established method for the preparation of chlorodeoxysugars. The conversion of a vicinal cis diol system to a cyclic sulfate in protected carbohydrates is readily accomplished with sulfuryl chloride. By using SO.sub.2 Cl.sub.2, the methyl 4,6-O-benzilidene-.beta.-D-mannopyranoside 2,3-cyclic sulfate, and 1,6-anhydro-4-O-benzyl-.beta.-D-mannopyranoside 2,3-cyclic sulfate [28] were obtained in 60% and 85% yield.
The reaction of diols with thionyl chloride (SOCl.sub.2) in the presence of an amino base gives cyclic sulfites directly and in good yield, unlike the analogous reaction with sulfuryl chloride (SO.sub.2 Cl.sub.2) which usually results in only very low yields of the corresponding cyclic sulfates. The ring strain energy (.about.5-6 kcal/mol) of 1,2 cyclic sulfates is most often cited as the reason of the very poor yields in their direct preparation from a diol and SO.sub.2 Cl.sub.2 (or SO.sub.2 X.sub.2).
Cyclic sulfates are readily prepared through the oxidation of cyclic sulfites. Permanganate oxidation of the sulfite was originally the favored route to cyclic sulfates. It has been reported that the oxidation step was much cleaner when effected by a stoichiometric amount of ruthenium(IV) tetraoxide (RuO.sub.4). Gao and Sharpless reported the use of a catalytic amount of ruthenium(III) trichloride (RuCl.sub.3) with NaIO.sub.4 as a preparative method for the synthesis of cyclic sulfates from cyclic sulfites. Various syntheses of cyclic sulfates of mannitol and mannosides, using this method, reportedly gave good yields.
Another approach for the synthesis of cyclic sulfites and sulfates from protected carbohydrates relies on the use of N,N'-thionyldiimidazole or N,N'-sulfuryldiimidazole, respectively. However, this chemistry requires the use of a strong base, such as NaH. Phenyl chlorosulfate has also been reported to give the corresponding cyclic sulfate of protected sugars in 60-70% yield. Only 1,2-cyclic sulfites of the unprotected carbohydrates, glucose, galactose and mannose have been synthesized using N,N'-thionylimidazole. These cyclic sulfites were reportedly unstable and were used in situ in the reaction with azide. Schmidt et al. recently reported the use of cyclic sulfate to prepare sugar-based surfactants. However, the cyclic sulfates synthesized from 1,2-fatty diols, were used for alkylation of glucose to obtain anomeric alkyl glycosides.
The regioselective introduction of fatty acyl groups into sucrose, either chemically or enzymatically, leads to surface active neutral sucrose esters. The synthesis of new sulfated surfactants in the present invention demonstrates the regioselective sulfonation of O-acylsucrose derivatives and the nucleophilic opening of an intermediate cyclic sulfate to prepare anionic and amphoteric sucrose-based surfactants.